Type 1 and Type 2 Epstein-Barr viruses induce proliferation, and inhibit differentiation, in infected telomerase-immortalized normal oral keratinocytes.

Differentiated epithelial cells are an important source of infectious EBV virions in human saliva, and latent Epstein-Barr virus (EBV) infection is strongly associated with the epithelial cell tumor, nasopharyngeal carcinoma (NPC). However, it has been difficult to model how EBV contributes to NPC, since EBV has not been shown to enhance proliferation of epithelial cells in monolayer culture in vitro and is not stably maintained in epithelial cells without antibiotic selection. In addition, although there are two major types of EBV (type 1 (T1) and type 2 (T2)), it is currently unknown whether T1 and T2 EBV behave differently in epithelial cells. Here we inserted a G418 resistance gene into the T2 EBV strain, AG876, allowing us to compare the phenotypes of T1 Akata virus versus T2 AG876 virus in a telomerase-immortalized normal oral keratinocyte cell line (NOKs) using a variety of different methods, including RNA-seq analysis, proliferation assays, immunoblot analyses, and air-liquid interface culture. We show that both T1 Akata virus infection and T2 AG876 virus infection of NOKs induce cellular proliferation, and inhibit spontaneous differentiation, in comparison to the uninfected cells when cells are grown without supplemental growth factors in monolayer culture. T1 EBV and T2 EBV also have a similar ability to induce epithelial-to-mesenchymal (EMT) transition and activate canonical and non-canonical NF-κB signaling in infected NOKs. In contrast to our recent results in EBV-infected lymphoblastoid cells (in which T2 EBV infection is much more lytic than T1 EBV infection), we find that NOKs infected with T1 and T2 EBV respond similarly to lytic inducing agents such as TPA treatment or differentiation. These results suggest that T1 and T2 EBV have similar phenotypes in infected epithelial cells, with both EBV types enhancing cellular proliferation and inhibiting differentiation when growth factors are limiting.

Flexibility in valenced reinforcement learning computations across development.

Optimal integration of positive and negative outcomes during learning varies depending on an environment's reward statistics. The present study investigated the extent to which children, adolescents, and adults (N = 142 8-25 year-olds, 55% female, 42% White, 31% Asian, 17% mixed race, and 8% Black; data collected in 2021) adapt their weighting of better-than-expected and worse-than-expected outcomes when learning from reinforcement. Participants made choices across two contexts: one in which weighting positive outcomes more heavily than negative outcomes led to better performance, and one in which the reverse was true. Reinforcement learning modeling revealed that across age, participants shifted their valence biases in accordance with environmental structure. Exploratory analyses revealed strengthening of context-dependent flexibility with increasing age.

Cyclin-Dependent Kinase-Mediated Phosphorylation of FANCD2 Promotes Mitotic Fidelity.

Fanconi anemia (FA) is a rare genetic disease characterized by increased risk for bone marrow failure and cancer. The FA proteins function together to repair damaged DNA. A central step in the activation of the FA pathway is the monoubiquitination of the FANCD2 and FANCI proteins, which occurs upon exposure to DNA-damaging agents and during the S phase of the cell cycle. The regulatory mechanisms governing S-phase monoubiquitination, in particular, are poorly understood. In this study, we have identified a cyclin-dependent kinase (CDK) regulatory phosphosite (S592) proximal to the site of FANCD2 monoubiquitination. FANCD2 S592 phosphorylation was detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and by immunoblotting with an S592 phospho-specific antibody. Mutation of S592 leads to abrogated monoubiquitination of FANCD2 during the S phase. Furthermore, FA-D2 (FANCD2-/-) patient cells expressing S592 mutants display reduced proliferation under conditions of replication stress and increased mitotic aberrations, including micronuclei and multinucleated cells. Our findings describe a novel cell cycle-specific regulatory mechanism for the FANCD2 protein that promotes mitotic fidelity.

Hexavalent chromium-reducing bacteria on biosolids from the San Fernando Wastewater Treatment Plant in Medellín (Colombia) / Bacterias aisladas de biosólidos de la PTAR San Fernando en Medellín-Colombia con capacidad para reducir cromo hexavalente

ABSTRACT During the most recent decades, advances have been made to reduce the environmental impact by anthropogenic activities that constantly release toxic components into the environment, generating instability and damage to the health of biological communities. Among the different pollutants, heavy metals are important by virtue of their properties, which hinder their degradation or transformation into other less toxic compounds. Chromium is one of the metals of greatest global interest due to its use in multiple industries. Conventional methods using chromed materials in their processes, not only throw considerable amounts of waste into the environment, but also give little account of the fraction of hexavalent chromium (Cr6+) present in certain ecosystems. Bioremediation has been proposed as an economically viable and environmentally sustainable alternative. This work aimed to evaluate the chromium reduction capacity by bacteria isolated from a biosolids matrix obtained at the San Fernando Wastewater Treatment Plant (WWTP), located in Medellín (Colombia). Biosolids samples were grown in a nutrient agar enriched with different concentrations of Cr6+. The strains presenting the greater tolerance to chromium were isolated to perform reduction tests by triplicate, monitoring the concentration of the metal over time. Seven different bacterial species were obtained, among which Staphylococcus saprophyticus, Ochrobactrum anthropic, and Bacillus cereus showed the greatest ability to reduce Cr6+ (29.0%, 61.1 and 100%, at 96 h) respectively.

RESUMEN En las últimas décadas se ha trabajado activamente para reducir el impacto ambiental generado por las actividades antrópicas que constantemente liberan componentes tóxicos al ambiente generando inestabilidad y daños en la salud de las comunidades biológicas. Entre los diferentes contaminantes, los metales pesados revisten importancia en virtud de sus propiedades, que dificultan su degradación o transformación en otros compuestos menos tóxicos. El cromo es uno de los metales de mayor interés a nivel global por su uso en múltiples industrias. Los métodos convencionales que utilizan materiales cromados en sus procesos, no sólo arrojan cantidades considerables de residuos al ambiente, sino que dan poca cuenta de la fracción de Cr6+ presente en determinados ecosistemas. La biorremediación se ha propuesto como una alternativa económicamente viable y ambientalmente sostenible. El propósito del presente trabajo fue evaluar la capacidad de reducción de cromo por bacterias, aisladas de una matriz de biosólidos de la Planta de tratamiento de aguas residuales (PTAR) San Fernando en la ciudad de Medellín-Colombia. Muestras de biosólidos se cultivaron en Agar Nutritivo enriquecido con diferentes concentraciones de Cr6+. Las cepas que presentaron mayor tolerancia al cromo fueron aisladas para realizar ensayos de reducción por triplicado, monitoreando la concentración del metal en el tiempo. Se obtuvieron siete especies bacterianas diferentes dentro de las cuales se destacaron Staphylococcus saprophyticus, Ochrobactrum anthropi y Bacillus cereus por la capacidad de reducir Cr6+ a 96 h con eficiencias de 29.0%, 61.1% y 100%, respectivamente.

FANCD2 Binding to H4K20me2 via a Methyl-Binding Domain Is Essential for Efficient DNA Cross-Link Repair.

Fanconi anemia (FA) is an inherited disease characterized by bone marrow failure and increased cancer risk. FA is caused by mutation of any 1 of 22 genes, and the FA proteins function cooperatively to repair DNA interstrand cross-links (ICLs). A central step in the activation of the FA pathway is the monoubiquitination of the FANCD2 and FANCI proteins, which occurs within chromatin. How FANCD2 and FANCI are anchored to chromatin remains unknown. In this study, we identify and characterize a FANCD2 histone-binding domain (HBD) and embedded methyl-lysine-binding domain (MBD) and demonstrate binding specificity for H4K20me2. Disruption of the HBD/MBD compromises FANCD2 chromatin binding and nuclear focus formation and its ability to promote error-free DNA interstrand cross-link repair, leading to increased error-prone repair and genome instability. Our study functionally describes the first FA protein chromatin reader domain and establishes an important link between this human genetic disease and chromatin plasticity.

Imaging patients with cardiac trauma.

In the United States, trauma is the leading cause of death among those who are 1-44 years old, with cardiovascular injuries representing the second most common cause of traumatic death after central nervous system injuries. Evaluation of trauma patients with suspected cardiac injury may be complex and include electrocardiography, measurement of cardiac biomarkers, and imaging examinations. Contrast material-enhanced computed tomography (CT) has become one of the most valuable imaging tools available for evaluating hemodynamically stable patients with suspected cardiac injury. The presence of hemopericardium, with or without cardiac tamponade, is one of the most significant findings of cardiac injury. Other complications that result from blunt cardiac injury, such as pericardial rupture and cardiac herniation, may be readily depicted at multidetector CT. Assessment of patients with cardiac injuries, particularly those with penetrating injuries, is a challenging and time-critical matter, with clinical and imaging findings having complementary roles in the formation of an accurate diagnosis. Patients who are hemodynamically stable, particularly those with penetrating cardiac injuries, also may benefit from a timely imaging examination. In addition to chest radiography, other available modalities such as transthoracic and transesophageal echocardiography, nuclear medicine, and magnetic resonance imaging may play a role in selected cases.